Additive effect of frequent polymorphism and rare synonymous variant alters splicing in twin patients with Niemann-Pick disease type C
| العنوان: | Additive effect of frequent polymorphism and rare synonymous variant alters splicing in twin patients with Niemann-Pick disease type C |
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| المؤلفون: | Vyacheslav Tabakov, S. A. Klyushnikov, Maria Karpova, Grigory Perelman, Alexandra Filatova, Ekaterina Zakharova, Igor Bychkov, Mikhail Skoblov, Alexandra Ilyushkina, Tatiana Yu. Proshlyakova, Daria Korotkova, Galina Baydakova |
| المصدر: | Eur J Hum Genet |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | congenital, hereditary, and neonatal diseases and abnormalities, Penetrance, Biology, Brief Communication, Polymorphism, Single Nucleotide, Frameshift mutation, 03 medical and health sciences, Exon, Niemann-Pick C1 Protein, Polymorphism (computer science), hemic and lymphatic diseases, Twins, Dizygotic, Genetics, medicine, Humans, Point Mutation, Frameshift Mutation, Cells, Cultured, Genetics (clinical), 0303 health sciences, Niemann–Pick disease, type C, 030305 genetics & heredity, Wild type, nutritional and metabolic diseases, Niemann-Pick Disease, Type C, Fibroblasts, Middle Aged, medicine.disease, Molecular biology, RNA Splice Sites, NPC1, Minigene |
| الوصف: | Niemann-Pick disease type C (NP-C) (OMIM#257220) is a rare lysosomal storage disorder caused by pathogenic variants in either the NPC1 or NPC2 genes. It manifests with a wide spectrum of clinical symptoms and variable age of onset. We studied the impact of the frequent polymorphic variant c.2793 C > T (p.Asn931 = ), located in the donor splice site (SS) of NPC1 exon 18 on the penetrance of the rare synonymous variant c.2727 C > T (p.Cys909 = ), identified in two 55 y.o. twins with an adult onset form of NP-C. The patients’ diagnosis was supported by biochemical analysis and positive filipin test. Analysis of the patients’ cDNA showed that the c.2727 C > T variant leads to cryptic donor SS activation and frameshift deletion in the NPC1 exon 18. However, the minigene assay demonstrated that this exon shortening takes place only in the presence of the frequent polymorphic variant c.2793 C > T. Results of the transcript specific qPCR showed that only the presence in the NPC1 exon 18 of both variants leads to significant decrease of wild type (WT) transcript isoform. |
| تدمد: | 1476-5438 1018-4813 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::10e93d5d7856ea13f4bfc3211a20f6e4 https://doi.org/10.1038/s41431-021-00898-7 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....10e93d5d7856ea13f4bfc3211a20f6e4 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14765438 10184813 |
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